The cough reflex is an important mechanism whereby secretions from the lungs and airways are removed. Generally, such secretions are removed by the mucociliary escalator. However, when this mechanism is defective, or becomes overwhelmed by, for example, excessive secretions, cough then becomes a principal means of secretion removal.
The cough reflex is initiated by stimulation of mechanical receptors and is controlled by afferent pathways within the vagus (X), glossopharyngeal (IX), and superior laryngeal nerves to the cough center in the brainstem. Cough can be caused by, for example, foreign bodies, dust, mucus, debris, gases and smoke in the lower respiratory tract. Irritation of various sensory nerves in the nose, sinuses, pharynx, ears, stomach, pericardium or diaphragm can also produce coughing. In many of these conditions, chronic or paroxysmal cough, however, can be exhausting and debilitating, particularly when it interferes with sleep.
Oral cough preparations, such as tablets, lozenges, syrups, solutions, suspensions and the like, containing an effective antitussive agent have long been used for the symptomatic relief of coughs. The most popular of such preparations contain either dextromethorphan (or its hydrobromide salt) or codeine (or its sulfate salt) as the active antitussive agent. These treatments, among many others, are fully described in Drug Evaluations, 6th Ed., Chapter 21 (The American Medical Association, 1986).
Generally, cough syrups and sore throat medications have been available as pourable liquids or thixotropic gels. Exemplary prior art gel formulations for treatment of cough including those disclosed in U.S. Pat. nO. 4,427,681, incorporated herein by reference which use a suspending agent (Avicel/R R-591 from FMC Corporation) that give a thixotropic character to the formulation that is very viscous and needs a special device or an appropriate amount of shear forces through a dispensing nozzle to pour.
However, due to the nature of the action of the various active ingredients present in such syrups and medications, Applicants have found that it is highly desirable to have compositions which contain a mucoadhesive such as a poly(ethylene oxide) with specific physical characteristics which coat and adhere to the throat and mucous membrane and can thereby maintain an active ingredient in more intimate contact with the irritated area. Without being limited to theory, Applicants believe such compositions provide protection to the mucosal surfaces and thereby can treat or reduce the irritation, pain and discomfort associated with laryngopharyngitis ("sore throat") as well as mucosal irritation associated with esophagitis.
Prior art compositions containing these adhesive materials for pharmaceutical and medical applications include osmotic dosage forms as disclosed in U.S. Pat. Nos. 4,816,263, 4,837,111, WO 91-07173 and Brit. Pat. Appl. GB 2,189,995; buccal drug dosage forms, as disclosed in U.S. Pat. No. 4,764368; topical compositions for treating Acne Vulgaris, as disclosed in U.S. Pat. No. 4,335,028; a dosage form for administering nilvadipine for treating cardiovascular symptoms as disclosed in U.S. Pat. No. 4,902,514; pharmaceuticals for oral cavities, as disclosed in U.S. Pat. No. 4,649,043 and Japan, Kokei: 86-69338; chorhexidine gel for preventing infection in patients with radiation therapy; multi-unit delivery systems ad disclosed in U.S. Pat. No. 5,023, 088; sustained release tablets, as disclosed in U.S. Pat. No. 4,404, 183 and EP 277092; oral capsule containing aqueous and oil to control gastrointestinal transit time, as disclosed in U.S. Pat. No. 4,690,82; and low melting moldable pharmaceutical excipient, Canadian patent 2000697.
It is, therefore, an object of the present invention to provide such vehicle compositions which coat and adhere to mucous membranes such as the throat. It is still a further object of the present invention to provide such compositions which can treat the irritation, pain and discomfort associated with laryngopharyngitis and esophagitis. A further object of the present invention is to provide such vehicle compositions which, when used with a pharmaceutical active maintain the active ingredient in more intimate contact with the oral mucosa. These and other objects of this invention will become apparent in light of the following.